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Comparison of the Virulent Asibi Strain of Yellow Fever Virus with the 17D Vaccine Strain Derived from It

Hahn, Chang S. and Dalrymple, Joel M. and Strauss, James H. and Rice, Charles M. (1987) Comparison of the Virulent Asibi Strain of Yellow Fever Virus with the 17D Vaccine Strain Derived from It. Proceedings of the National Academy of Sciences of the United States of America, 84 (7). pp. 2019-2023. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:HAHpnas87

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Abstract

We have sequenced the virulent Asibi strain of yellow fever virus and compared this sequence to that of the 17D vaccine strain, which was derived from it. These two strains of viruses differ by more than 240 passages. We found that the two RNAs, 10,862 nucleotides long, differ at 68 nucleotide positions; these changes result in 32 amino acid differences. Overall, this corresponds to 0.63% nucleotide sequence divergence, and the changes are scattered throughout the genome. The overall divergence at the level of amino acid substitution is 0.94%, but these changes are not randomly distributed among the virus proteins. The capsid protein is unchanged, while proteins NS1, NS3, and NS5 contain 0.5% amino acid substitutions, and proteins ns4a and ns4b average 0.8% substitutions. In contrast, proteins ns2a and ns2b have 3.0 and 2.3% amino acid divergence, respectively. The envelope protein also has a relatively high rate of amino acid change of 2.4% (a total of 12 amino acid substitutions). The large number of changes in ns2a and ns2b, which are largely conservative in nature, may result from lowered selective pressure against alteration in this region; among flaviviruses, these polypeptides are much less highly conserved than NS1, NS3, and NS5. However, many of the amino acid substitutions in the E protein are not conservative. It seems likely that at least some of the difference in virulence between the two strains of yellow fever virus results from changes in the envelope protein that affect virus binding to host receptors. Such differences in receptor binding could result in the reduced neurotropism and vicerotropism exhibited by the vaccine strain.


Item Type:Article
Additional Information:Copyright © 1987 by the National Academy of Sciences Communicated by Ray D. Owen, November 17, 1986 (received for review October 30, 1986) We thank Ms. E. M. Lenches for expert technical assistance. This work was supported by a grant from The World Health Organization and in part by Grants AI 20612 and AI 10793 from the National Institutes of Health and Grant PCM 83 16856 from the National Science Foundation. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Record Number:CaltechAUTHORS:HAHpnas87
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:HAHpnas87
Alternative URL:http://www.pnas.org/cgi/content/abstract/84/7/2019
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ID Code:4913
Collection:CaltechAUTHORS
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Deposited On:12 Sep 2006
Last Modified:26 Dec 2012 09:02

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